Skip to main content
eScholarship
Open Access Publications from the University of California
Refine Search

Lawrence Berkeley National Laboratory

Recent Work bannerLawrence Berkeley National Laboratory

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.

  • Author(s): Schoof, Michael;
  • Faust, Bryan;
  • Saunders, Reuben A;
  • Sangwan, Smriti;
  • Rezelj, Veronica;
  • Hoppe, Nick;
  • Boone, Morgane;
  • Billesbølle, Christian B;
  • Puchades, Cristina;
  • Azumaya, Caleigh M;
  • Kratochvil, Huong T;
  • Zimanyi, Marcell;
  • Deshpande, Ishan;
  • Liang, Jiahao;
  • Dickinson, Sasha;
  • Nguyen, Henry C;
  • Chio, Cynthia M;
  • Merz, Gregory E;
  • Thompson, Michael C;
  • Diwanji, Devan;
  • Schaefer, Kaitlin;
  • Anand, Aditya A;
  • Dobzinski, Niv;
  • Zha, Beth Shoshana;
  • Simoneau, Camille R;
  • Leon, Kristoffer;
  • White, Kris M;
  • Chio, Un Seng;
  • Gupta, Meghna;
  • Jin, Mingliang;
  • Li, Fei;
  • Liu, Yanxin;
  • Zhang, Kaihua;
  • Bulkley, David;
  • Sun, Ming;
  • Smith, Amber M;
  • Rizo, Alexandrea N;
  • Moss, Frank;
  • Brilot, Axel F;
  • Pourmal, Sergei;
  • Trenker, Raphael;
  • Pospiech, Thomas;
  • Gupta, Sayan;
  • Barsi-Rhyne, Benjamin;
  • Belyy, Vladislav;
  • Barile-Hill, Andrew W;
  • Nock, Silke;
  • Liu, Yuwei;
  • Krogan, Nevan J;
  • Ralston, Corie Y;
  • Swaney, Danielle L;
  • García-Sastre, Adolfo;
  • Ott, Melanie;
  • Vignuzzi, Marco;
  • QCRG Structural Biology Consortium;
  • Walter, Peter;
  • Manglik, Aashish
  • et al.

Published Web Location

https://doi.org/10.1126/science.abe3255
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View


Top